About 50% of children who are patients in Pediatric Special Care Units require some form of total or supplemental parenteral nutrition. The need for and the composition of nutritional support therapy are determined on the basis of clinical judgment because no simple specific tests are available to assess the metabolic state of infants. Inadequate parenteral nutrition will not prevent malnutrition with slow development and permanent brain damage. Excessive administration of protein fluids causes metabolic acidosis, hyperammonemia and hyperaminoacidemia. In the present study, we propose to use the urinary 3-methylhistidine (3MH) to creatinine ratio to evaluate protein metabolism in infants. The validity of the 3MH/creatinine ratio has already been established in animals and human adults and in our preliminary experiments in human infants. In the first part of the proposed study we will establish normal values for 3MH/creatinine ratios in 125 healthy, growing infants (75 premature, 25 term and 25 small-for-gestational-age infants). In the second part we will study 100 infants who receive nutritional support and have a variety of clinical conditions including respiratory distress syndrome, sepsis, congestive heart failure, gastrointestional dysfunction and abdominal surgery, changes in weight, length and head circumference will be followed in all patients and daily nitrogen balance will be determine in the ill patients. Comparison of the 3MH/creatinine ratios to the growth curves and to the nitrogen balances will allow us to determine the 3MH/ creatinine ratio which is consistent with adequate nutrition and positive nitrogen balance. One of us (JHS) has previously shown that a positive nitrogen balance of 0.2 gm/kg/day is sufficient for normal growth.